Uptake and metabolism of biogenic amines in developing lung were studied in a total of 62 New Zealand White rabbits aged 28 days of gestation to 28 days postnatal. Lungs were perfused in vitro with 5-[14C]hydroxytryptamine (5-HT) or [14C]phenylethylamine (PEA) and coperfused with high-molecular-weight [3H]dextran to assess the vascular space perfused. Patterns of uptake and metabolism of PEA and 5-HT as functions of age were markedly different. PEA uptake and metabolism gradually increased with advancing age. No differences were observed in 5-HT uptake or metabolism within the postnatal age range studied, but the magnitude of each process for 5-HT was significantly lower in premature animals. Functional maturity for both uptake and metabolism of PEA was observed by 14-21 days of age. Inhibition of intrapulmonary monoamine oxidase by semicarbazide and pargyline showed that PEA metabolism was unaffected by the former and moderately reduced by the latter agent only in animals older than 1 wk. Thus the lung of the newborn rabbit effectively takes up and metabolizes PEA and 5-HT, but age-related differences are evident in the development of specific monoamine oxidase subtypes. Reduced 5-HT metabolism in lung of premature animals paralleled changes in the measured vascular space, possibly reflecting difficulty in perfusing premature lungs as well as immature functional status. This study emphasizes the importance of determining functional vascular perfusion (by coperfusion with intravascular markers) when studying the developing lung.